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EP 0 966 022 B1 |
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EUROPEAN PATENT SPECIFICATION |
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Mention of the grant of the patent: |
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30.05.2007 Bulletin 2007/22 |
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Date of filing: 17.06.1999 |
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International Patent Classification (IPC):
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Multi-inlet mass spectrometer
Mehrfachprobeninlassmassenspektrometer
Spectromètre de masse à introduction multiple d'échantillons
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Designated Contracting States: |
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BE DE FR GB IT NL SE |
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Priority: |
18.06.1998 GB 9813225 27.07.1998 GB 9816342
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Date of publication of application: |
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22.12.1999 Bulletin 1999/51 |
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Proprietor: Micromass UK Limited |
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Manchester M22 5PP (GB) |
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Inventors: |
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- Bateman, Robert Harold
Knutsford,
Cheshire WA16 8BH (GB)
- Hickson, John Anthony David
London W2 3HG (GB)
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Representative: Jeffrey, Philip Michael |
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Frank B. Dehn & Co.
St Bride's House
10 Salisbury Square London EC4Y 8JD London EC4Y 8JD (GB) |
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References cited: :
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- PATENT ABSTRACTS OF JAPAN vol. 1998, no. 08, 30 June 1998 (1998-06-30) & JP 10 074480
A (NKK CORP), 17 March 1998 (1998-03-17)
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Note: Within nine months from the publication of the mention of the grant of the European
patent, any person may give notice to the European Patent Office of opposition to
the European patent
granted. Notice of opposition shall be filed in a written reasoned statement. It shall
not be deemed to
have been filed until the opposition fee has been paid. (Art. 99(1) European Patent
Convention).
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[0001] This invention relates to mass spectrometers wherein the process of ionizing a sample
involves the generation of a jet of charged particles. More particularly, it relates
to mass spectrometers for the analysis of liquid samples by electrospray or atmospheric
pressure ionization, but is also applicable to certain other types.
[0002] Complex mixtures of high molecular weight and/or thermally labile biomolecules are
now routinely analyzed by electrospray or atmospheric pressure ionization mass spectrometry,
often following separation by liquid chromatography or capillary electrophoresis.
Most conveniently, to carry out such analyses the eluent from the chromatographic
apparatus is fed directly to the electrospray or atmospheric pressure ionization source
of a mass spectrometer. Both these ionization techniques are capable of generating
intact molecular ions of very high molecular weight samples, and especially in the
case of electrospray ionization, these ions may carry a large number of charges. This
brings their mass-to-charge ratio into the range where it can be measured by relatively
inexpensive mass analyzers such as quadrupoles or ion traps.
[0003] Both electrospray and atmospheric pressure ionization sources used for the analysis
of solutions (rather than gases) involve the generation of a jet of charged particles
in a region of high ambient pressure (typically atmospheric) and means for passing
at least some of the charged particles into a region of lower pressure where they
are mass analyzed. The jet typically comprises an aerosol of droplets produced from
the solution, and the droplets may be at least partially desolvated by collisions
with inert gas molecules in the region of high pressure.
[0004] In the case of an electrospray ionization source the aerosol is formed by maintaining
a potential difference of between 3 and 6kV between the exit of a capillary tube containing
the solution to be analyzed and a counter electrode disposed downstream of it. The
droplets comprised in the aerosol are electrically charged and are at least partially
desolvated by collisions with molecules of an inert gas (usually heated) which is
caused to flow through the region where the aerosol is formed. The charged particles
so produced then pass through a nozzle-skimmer pressure reduction stage into an evacuated
region where they are mass analyzed. In the case of many biomolecules the ions produced
by electrospray ionization carry a large number of charges so that their mass-to-charge
ratios may lie in the mass range of a quadrupole mass analyzer of moderate cost which
could not be used if the ions were singly charged. Prior electrospray ionization sources
are disclosed in US patents 4,531,056, 4,542,293, 4,209,696, 4,977,320 and 5,504,327,
PCT Patent Applications 95/24259, 98/11595 and 97/29508 and UK Patent Application
2,308,227.
The technique of electrospray ionization has been reviewed by Fenn et. al. in Mass
Spectrom. Rev. 1990, vol 9 pp 37-70 and Smith et. al. in Mass Spectrom. Rev. 1991
vol 10 pp 359-451.
[0005] Historically, API sources were developed for the analysis of trace materials in gases
(for example, the source described in UK Patent 1,584,459), but are now extensively
used for the analysis of liquids. In such a source the jet of charged particles is
generated by first producing an aerosol of droplets from the solution by means of
a nebulizer in a region of high ambient pressure, then charging the droplets by a
separate ionization process, for example a corona discharge maintained between electrodes
in the vicinity of the aerosol. Charged droplets so produced may be desolvated as
in the case of an electrospray source and the charged particles so produced. See,
for example, Horning, Carroll et al, J Chromatog. 1974 vol 99 pp 13-21. Instead of
a corona discharge, other forms of ionization can be employed, for example a
63Ni radioactive foil, and many different types of nebulizer may be used. More recent
ion sources based on these early devices are known as atmospheric pressure chemical
ionization sources (APCI) because ionization is essentially a chemical ionization
process, that is, the reaction of sample molecules with primary ions generated in
the discharge or other means of primary ionization. In fact, a separate ionization
process is not always required and in some ion sources the nebulization step itself
generates a charged particle jet as a result of ion evaporation from the droplets
which become electrically charged during their formation from the bulk liquid.
[0006] A further variation of API sources is known as thermospray ionization, in which the
liquid is nebulized by causing it to flow through a strongly heated capillary tube.
(See for example US Patent 4,730,111). This nebulization method often produces sufficient
ions for subsequent mass analysis without an additional ionization step but may be
assisted by a variety of methods such as a glow discharge or electron impact ionization.
[0007] Ion sources that provide combinations of the features described, for use either simultaneously
or as alternative nebulization or ionization methods in the same source, are also
known. For example, most electrospray ion sources in current production also provide
APCI capabilities. See, for example, Andrien and Boyle, Spectroscopy 1995 vol. 2 pp.
42-44, PCT patent applications 95/24259 and 98/11595 and GB patent application 2,308,227.
[0008] Charged particle jet sources of the types described are very frequently used to analyze
the eluent from a liquid chromatograph, and are now employed in this way on a routine
basis. The ability of these sources to interface directly to liquid chromatography
and to produce characteristic ions from very high mass mass thermally labile molecules
has recently created a demand for automated systems capable of analyzing many samples
in as short a time as possible, for example in medical screening programs (for example,
see Rasheed, Bucknall et al, Clin. Chem. 1997 vol 43:7 pp 1129-1141) and for DNA and
protein sequencing (for example, PCT patent application 94/16101). Applications of
this type require very high throughput if they are to be cost effective, but prior
types of charged-particle source are capable of accepting the eluent of a single chromatograph
only. An automatic flow-switching valve arrangement for a liquid chromatograph attached
to an API source is taught by Hagiwara et al. (J. Mass Spectrom. Sec. Japan, 1996
vol 44 (2) pp 249-259) but this is intended to reduce contamination of the ion source
during repeated analysis carried out by one chromatograph.
[0009] An electrospray ion source having several capillaries operating simultaneously is
reported by Kostiainen and Brums (Rapid Commun. in Mass Spectrometry, 1994 vol 8 pp
549-58) but this apparatus is intended to improve ionization efficiency from a single
flow of analyte. Andrien, Whitehouse, et. al, in PCT patent application WO 99/13492
(published 18 March 1999) describe a multiple inlet electrospray/API mass spectrometer
in which at least two of the solutions introduced are simultaneously ionized. The
mixture of ions generated from the two solutions is then introduced into a mass analyzer.
However, such simultaneous introduction inevitably results in mass spectral data that
represents a mixture of the two solutions and the method is therefore limited in its
applicability.
[0010] It is an object of the present invention, therefore, to provide a mass spectrometer
comprising a charged-particle jet ionization source that is capable of receiving a
plurality of fluid streams, each comprising a sample to be analyzed, without simultaneously
introducing ions from more than one of the fluid streams into the mass analyzer of
the spectrometer. It is another object of the invention to provide such a spectrometer
that can produce mass spectral data from all of the streams quickly enough to allow
the analysis of species in the streams that have been separated by high resolution
liquid chromatography.
[0011] It is further object to provide methods of mass spectrometry using a charged-particle
jet ionization source to analyze a plurality of fluid streams without simultaneously
introducing ions from more than one of the streams into a mass analyzer. Another object
of the invention is to provide such methods that are fast enough to allow the analysis
of species in the fluid streams that have been separated by high resolution liquid
chromatography. Further objects of the invention are to provide mass spectrometers
comprising electrospray, thermospray and/or APCI ion sources capable of analyzing
more than one flow of fluid and methods of operating those mass spectrometers. It
is yet another object to provide a liquid chromatograph mass spectrometer comprising
a plurality of chromatographs which can be operated simultaneously and still another
object to provide methods of operating it.
[0012] In accordance with these objectives the invention provides a mass spectrometer comprising
an evacuated chamber, a sampling region where the pressure is greater than in said
evacuated chamber, a sampling orifice communicating between said sampling region and
said evacuated chamber, and a mass analyzer which receives at least some charged particles
which pass along a first axis through said sampling orifice from said sampling region
into said evacuated chamber, said spectrometer characterized by the further provision
of:-
- a) a plurality of charged-particle jet generation means each of which is supplied
with a fluid to be analyzed and generates a jet, aligned with a jet axis, of charged
particles derived from said fluid, disposed so that each generation means has a different
jet axis and so that all said jet axes intersect said first axis within said sampling
region;
- b) jet selecting means comprising a hollow member disposed so that the intersections
of said jet axis and said first axis are within its interior, said hollow member having
at least a first aperture alignable with said jet axis through which at least some
charged particles comprised in a said charged-particle jet may enter the interior
of said hollow member and travel to said first axis; and
- c) means for aligning said aperture in said hollow member with each said jet axis
in turn, thereby allowing in turn at least some charged particles comprised in each
said jet to enter the interior of said hollow member to pass through said sampling
orifice into said evacuated chamber, and subsequently to enter said mass analyzer.
[0013] In preferred embodiments at least a second aperture is provided in the hollow member
of said jet-selecting means through which a charged particle jet entering through
the first aperture may exit from the interior after intersecting the first axis. In
this way the charged-particle jet suffers minimal disturbance when it selected.
[0014] In a further preferred embodiment the invention provides an electrospray ionization
mass spectrometer in which at least one said charged-particle jet generation means
comprises an aerosol generation means maintained at a high potential relative to counter
electrode means disposed downstream of it. Said counter electrode means may conveniently
comprise said hollow member which may be made of an electrically conductive material,
and/or an additional counter electrode disposed in the path of the jet of charged
particles which exits from said hollow member when the apertures in it are aligned
with the jet axis of the aerosol generation means. Said aerosol generation means may
comprise a capillary tube. Preferably, a nebulizing gas is supplied to the exit of
the capillary tube by means of a tube coaxial with the capillary tube to assist with
the formation of the aerosol, as in prior types of single-jet electrospray sources.
A heated drying gas may also be supplied to the exit of the aerosol generation means
in said sampling region to assist desolvation of the droplets produced in the aerosol.
[0015] In an alternative embodiment an atmospheric pressure ionization mass spectrometer
is provided, in which each charged-particle generation means comprises aerosol generation
means for generating droplets from said fluid and means for electrically charging
the droplets so produced. Aerosol heating means may also be provided for desolvating
the droplets produced by the aerosol generating means. Conveniently the means for
electrically charging the droplets may comprise a discharge electrode disposed in
said sampling region and maintained at a potential which results in the formation
of a corona discharge. The aerosol generating means may comprise a tube for supplying
a nebulizing gas, as in the case of the electrospray jet generation means described
above.
[0016] It is not necessary for all of the charged particle jet generation means to be identical.
It is within the scope of the invention to use, for example, two electrospray ionization
generation means and two atmospheric pressure ionization generation means. Further,
one or more of the charged-particle jet generation means may comprise a thermospray
ionization device, wherein ionization of the sample is effected by strongly heating
a capillary tube through which the sample solution is flowing.
[0017] It is also advantageous to use one of the charged particle jet generation means to
introduce a calibration compound for the mass spectrometer. In this way the mass spectrometer
calibration may be updated during each sampling cycle and the mass measurement accuracy
of the mass spectrometer consequently improved.
[0018] In further preferred embodiments the charged-particle jet generation means are radially
disposed so that the jets they produce are directed towards said first axis, the means
for aligning said aperture may comprise motor means for rotating said hollow member
to bring an aperture in line with each of the charged-particle jet generation means
in turn. Conveniently, the jets may be arranged to be perpendicular to the first axis,
but this is not essential. This radial disposition allows at least some of the charged
particles produced by each generation means to pass through the sampling orifice and
be analyzed by the mass analyzer. If, as is preferred, more than one aperture is provided,
these are typically arranged as diametrically opposed pairs so that in any given position
of the hollow member where one aperture is aligned with one of the charged-particle
generation means the other aperture of the pair provides an exit aperture through
which the charged-particle jet may escape from the hollow member with minimal disturbance.
In a preferred embodiment, two apertures are provided disposed directly opposite to
one another and the hollow member is rotated to align the apertures in it with a particular
jet axis.
[0019] The charged-particle jet generation means may be disposed around an arc of less than
180° centered on said first axis. As the hollow member rotates, one aperture in it
serves first to allow charged particles from each jet in turn to enter the hollow
member while the other serves as a corresponding exit aperture. Further rotation of
the hollow member then reverses the role of the two apertures so that the aperture
previously serving as the exit aperture then becomes the entrance aperture during
the next 180° of rotation of the hollow member. It will be appreciated that more apertures
can be provided if desired, providing that the arc around which the charged-particle
jet generators are arranged is less than the angle between adjacent apertures in the
hollow member.
[0020] Further preferably movement of the hollow member is stopped for a predetermined time
period when an aperture in it is aligned with each of the charged-particle jet generation
means in turn. This allows charged particles to be sampled from each generation means
in turn for the predetermined time period without interference from the charged particles
produced by the other generation means. Relevant data from the mass spectrometer is
then acquired only while a particular charged particle jet is being sampled. Means
may be produced for associating the data being acquired with the generation means
being sampled at that time, for example by detecting the position of the jet selection
means and flagging the corresponding data accordingly.
[0021] Apparatus according to the invention may also comprise a plurality of chromatographs,
each feeding its eluent to a different charged-particle jet generation means. Typically,
liquid chromatographs will be used in conjunction with electrospray ionization, but
gas chromatographs or capillary electrophoresis separation devices may also be employed
. Using four such chromatographs and their corresponding generation means disposed
at 45° to each other, a jet selection means comprising two apertures may sample each
chromatograph eluent for 0.1 seconds and take 0.1 seconds to move between each of
the generation means. Thus a complete mass spectrum may be generated for every chromatograph
more frequently than once per second while four chromatographic analyses are being
carried out.
[0022] Any convenient type of mass analyzer may be used in the invention, for example, magnetic
sector, quadrupole, ion trap or time-of-flight analyzers , and tandem mass spectrometers
such as triple-quadrupole mass spectrometers. Time-of-flight and ion-trap mass analyzers
are especially appropriate because of their ability to substantially simultaneously
detect ions of all mass-to-charge ratios. Consequently, an undistorted complete spectrum
can be recorded in a shorter time while the jet selection means is sampling charged
particles from any particular jet generation means than would be possible with a scanning
mass analyzer. The data so acquired may then be processed in the time period when
the jet selection means is moving between the generation means so that the analyzer
is able to start acquisition as soon as the jet selection means is aligned with the
next generation means. In this way it is possible to speed up the rate at which each
of the jet generation means is sampled, thereby minimizing the loss of time-varying
data from each of the generation means. However, tandem mass spectrometers, especially
triple-quadrupole mass spectrometers, also benefit from the greater sample throughput
that can be achieved using the present invention.
[0023] Viewed from another aspect the invention provides a method of mass spectrometry comprising
mass analyzing charged particles which pass into an evacuated chamber through a sampling
orifice along a first axis from a sampling region in which the pressure is greater
than in the evacuated chamber, said method characterized by:-
- a) supplying a fluid to be analyzed to each of a plurality of charged-particle jet
generator means to generate jets of charged particles derived from said fluid along
a jet axis, each said charged-particle jet generation means having a different jet
axis and each said jet axis intersecting said first axis within said sampling region;
and
- b) selecting in turn each of at least some of the jets of charged-particles by aligning
with them a first aperture in a hollow member within whose interior said jet axis
and said first axis intersect so that charged particles comprised in the jet so selected
may enter the interior of said hollow body and travel to said first axis and at least
some of said charged-particles pass along said first axis through said sampling orifice
into said evacuated chamber.
[0024] A preferred method further comprises allowing said selected jet to exit through a
second aperture in said hollow member. In other preferred methods the jet of charged
particles is produced by electrospray ionization, for example by generating an aerosol
of droplets at a high potential relative to counter electrode means disposed downstream
of the charged-particle jet generation means. Alternatively, or in addition, the jet
of charged particles may be produced by atmospheric pressure ionization, for example
by generating an aerosol and electrically charging the droplets so produced by means
of a corona discharge.
[0025] Further preferred methods according to the invention comprise repeating the cycle
of mass analyzing in turn each of at least some of said jets of charged particles
and acquiring mass spectral data for each selected jet of charged particles during
a plurality of said cycles. In preferred methods the step of mass analyzing the charged
particles comprises measuring their mass-to-charge ratios using a time-of-flight or
an ion trap mass analyzer, but tandem mass analyzers, such as a triple-quadrupole
can also be used. Still further preferred methods comprise selecting a said jet of
charged particles for a predetermined time by maintaining said hollow member in a
fixed position and acquiring mass spectral data for said predetermined time, then
aligning said hollow member to select the next of said jets of charged particles for
which mass spectral data acquired, inhibiting the acquisition of data while said alignment
is taking place.
[0026] Typically, the fluid supplied to each of the charged-particle jet generation means
comprises the eluent from a chromatograph. Thus the invention provides a method of
carrying out simultaneously the mass spectral analysis of the eluent from a plurality
of chromatographs without the need for a plurality of mass spectrometers or switching
the eluent flows directly.
[0027] Preferred embodiments of the invention will now be described in greater detail by
reference to the figures, in which:
Figure 1 is a sectional schematic drawing of a time-of-flight mass spectrometer according
to the invention;
Figure 2 is a drawing of a jet selection means suitable for use in the spectrometers
illustrated in figures 1 and 6;
Figure 3 is a drawing of a charged-particle jet generation means suitable for use
in the spectrometers illustrated in figures 1 and 6;
Figure 4 is a drawing showing an atmospheric pressure ionization jet generation means
suitable for use in the spectrometers illustrated in figures 1 and 6;
Figure 5 is a drawing showing more details of the jet selection means of figure 2;
Figure 6 is an outline drawing of a triple quadrupole tandem mass spectrometer according
to the invention; and
Figure 7 is a drawing of an alternative jet selection means suitable for use in the
spectrometers of figures 1 and 6.
[0028] Referring first to figure 1, a mass spectrometer according to the invention comprises
a plurality of charged-particle jet generation means (one of which is shown at 1)
which generate a jet of charged particles 2 along a jet axis 3 (see also figure 2)
and a jet selection means generally indicated by 4, described in more detail below.
A sampling orifice 5 formed in the apex of a cone 6 provides communication between
a sampling region 7 and an evacuated chamber 8 formed in a sampling body 9. The evacuated
chamber 8 is evacuated through an extraction region 10, via the passageways 11 and
12 and the port 13 and is maintained at a pressure of between about 1,3 and 6,7 x
10
2 Pa (1 and 5 mmHg). A hollow conical member 14 is fitted in an adapter 15 (made from
a filled PTFE such as PEEK) to which the sampling body 9 is attached. The hollow conical
member 14 comprises an orifice in its apex through which charged particles may pass
from the extraction chamber 10 into its interior. An insulating washer 16 prevents
electrical contact between the hollow conical member 14 and the sampling body 9, allowing
a potential difference to be maintained between the body 9 and the hollow conical
member 14. The interior of the hollow conical member 14 is in communication with a
second evacuated chamber 17 which is evacuated by a vacuum pump 18 and contains a
hexapole ion guiding device 19. Chamber 17 is maintained at about 1,3-0,13 Pa (10
-2-10
-3 mm Hg) by the pump 18. Ions which pass from the extraction region 10 through the
hollow conical member 14 are then transmitted through the guiding device 19 through
an orifice 20 into a third evacuated chamber 22 maintained at a pressure of less than
10
-5 mm Hg by a vacuum pump 23. Conveniently, the guiding device 19 may comprise an RF-only
hexapole ion guide which results in optimum ion transmission without significant mass
discrimination, but other types of ion guides can also be used. A conventional orthogonal-acceleration
time-of-flight mass analyzer comprising an ion pusher 24, a drift region 25, an ion
reflector 26 and an ion detector 27 is contained within the third evacuated region
22. Ions entering the third evacuated chamber 22 through the orifice 20 are focussed
into the ion pusher 24 by an electrostatic lens 21. Ion ejection pulses are supplied
to the ion pusher 24 by a pulse generator 28 controlled by an analyzer controller
29 which also receives a signal from the ion detector 27 via the detector signal processor
63. A digital computer 30 is provided for processing the data generated by the time-of-flight
mass analyzer and controlling the complete spectrometer. Operation of the time-of-flight
mass analyzer is conventional.
[0029] A heater 64 enclosed by a cover 65 is attached to the sampling body 9 and is used
to maintain the sampling body 9 at any desired temperature. For the analysis of thermally
labile samples such as proteins a temperature of about 70°C is suitable, but higher
temperatures, up to approximately 150°C, may be beneficial for more stable samples.
[0030] When the jet selection means 4 is positioned so that apertures in it are aligned
with one of the jet axes 3, charged particles produced by one of the selected charged-particle
jet generation means I pass through the sampling region 7. In the embodiment shown
in figure 1 the jet generation means 1 comprises an electrospray probe (shown in greater
detail in figure 3), the capillary of which is maintained at a high potential relative
to a counter electrode which comprises the hollow member 36 (part of the jet selection
means 4) by means of a power supply 35, thereby generating an electrosprayed jet of
charged particles 2 in the sampling region 7. At least some of these charged particles
enter the first evacuated chamber 8 through the orifice 5 along a first axis 37, then
pass into the extraction region 10 and are subsequently mass analyzed, as explained.
[0031] Referring next to figure 2, which shows the jet selection means 4 in greater detail,
four electrospray jet generation means 1, 38-40 are disposed at 45° to one another
so that their tips are arranged on an arc centered on the axis 37 (figure 1). The
jet generation means are disposed in a plane 41 (figure 1), perpendicular to the first
axis 37. In this embodiment, the hollow body member 36 (see below) serves as a counter
electrode for each of the electrospray jet generation means 1, 38-40, and no additional
counter electrodes are provided. However, in other embodiments counter electrodes
may be provided, for example in the position indicated by the dotted box 34 for the
jet generation means 1. Each jet generation means is continuously supplied with a
fluid to be analyzed and generates a continuous electrospray along jet axis 3, 45-47
respectively. As can be seen, each jet generation means 1 has a different jet axis
3, and all the jet axes intersect the first axis 37 in the sampling region 7.
[0032] An electrically-conductive hollow member 36 of substantially cylindrical form comprises
two apertures 48, 49 through which each jet axis 3, 45-47 may pass when the member
36 is aligned with them, permitting charged particles from the selected electrospray
jet generation means to pass into the sampling region 7. The sampling region 7 will
of course be at a pressure above that of the evacuated chamber 8. It may be at atmospheric
pressure, or, especially in the case of electrospray sources, somewhat above or below
atmospheric pressure. Baffle tubes 50 are provided on the hollow member 36 to ensure
that material from the unselected jet generation means does not enter the sampling
region 7.
[0033] The hollow member 36 is mounted on the shaft 51 of a stepping motor 52 and supported
by a bearing 53 mounted on a bracket 54, as shown in figure 1. Motor 52 is controlled
by a motor controller 55 which in turn is controlled by the computer 30.
[0034] In use, once the four electrospray jets are established, the computer 30 causes the
stepping motor 52 to rotate the hollow member 36 until its apertures are aligned with
the jet axis 3 associated with the charged-particle jet generation means 1 so that
the jet 2 of charged particles it produces enters the sampling region 7. At least
some of the charged particles in the jet 2 then pass through the orifice 5 and are
mass analyzed. The computer 30 is programmed to hold the hollow member 36 in this
position for a predetermined time (typically 0.1 seconds) while mass spectral data
is stored, after which it advances the hollow member so that its apertures are aligned
with the jet axis 45 associated with the charged-particle jet generation means 38,
and again holds the hollow member in position while mass spectral data is acquired.
During the time while the hollow member is actually moving, computer 30 processes
the data acquired from the detector signal processor 63 so that the mass analyzer
is ready to acquire data as soon as the hollow member is aligned with the next jet
axis.
[0035] The rotation and pause cycle of the hollow member continues until each of the charged-particle
jet generation means has been sampled, and the whole process is repeated, storing
the mass spectral data in synchronism with the rotation of the hollow member. In this
way, mass spectral data for each of the separate fluids fed to the charged-particle
jet generation means may be acquired over an extended time period.
[0036] An electrospray jet generation means 1 suitable for use with the invention is shown
in figure 3. It comprises a hollow probe shaft 81 made of a rigid insulating material
comprising a flange 82 which is located in a recess in the end wall 66 of a cylindrical
housing 67. A stainless steel shaft extension 68 is sealed into the end of the shaft
64 by means of a 'O' ring 69, and a hollow stainless steel tip 70 is sealed into the
end of the extension 68 by means of a second 'O' ring 71. A narrow bore small diameter
capillary tube 72, also of stainless steel, runs the entire length of the probe assembly
and is connected at the end remote from the tip 70 to a source of the solution to
be analyzed, for example a liquid chromatographic column.
[0037] A supply of nebulizing gas (e.g., nitrogen) is fed via the pipe 73 to a 'T' connector
74 which is attached by a clamp 75 to a support plate 76 fixed in the housing 67.
The capillary tube 72 passes straight through the remaining two unions on the 'T'
connector 74 and is sealed in the union 77. A length of larger bore tube 78 through
which the capillary tube 72 passes without a break, is sealed in the union 79 on the
'T' connector 74 and extends through the hollow interiors of the probe shaft 81, the
shaft extension 68, and the probe tip 70. The capillary tube 72 protrudes about 0.5
mm from the end of the tube 78 so that the nebulizing gas emerges from the tube 78
and assists the electrostatic nebulization of the solution emerging from capillary
tube 72.
[0038] In order to cause the electrospray ionization, the electrospray power supply 35 (Fig.
1) is connected to the 'T' connector 74 by the lead 80 so that the connector and the
tubes 78 and 72 are maintained at the electrospray potential. A drying gas, typically
heated nitrogen, is introduced into the sampling region 7 through a pipe 31 in order
to assist the desolvation of the aerosol produced by the electrospray jet generation
means, as in conventional electrospray ionization sources.
[0039] As explained, the charged-particle jet generation means 1, 38-40 may comprise an
atmospheric pressure ionization jet generation means instead of an electrospray ionization
jet generation means. Figure 4 shows such a generation means. A coaxial flow nebulizer
56 (similar to the arrangement shown in figure 3) and an aerosol heating means comprising
a strongly heated tube 59 produce an aerosol in the sampling region 7 whenever the
apertures in the jet selection means 4 are aligned with it. A corona discharge is
produced in the sampling region 7 (when the nebulizer 56 is selected) by means of
a high potential applied to a discharge electrode 58 (also shown in figure 5). Charged
particles produced in the discharge travel along the jet axis 57 to the interior of
the hollow member 36 as does the electrospray shown in figures 1 and 2. Jet generation
means according to figure 4 may replace any or all of the jet generation means 1,
38-40 of figure 2.
[0040] Figure 5 shows in more detail the hollow member 36. It comprises an electrically
conductive open-ended cylinder 60 to which two diametrically opposed baffle tubes
50 are attached as shown. The cylinder 60 is supported on the shaft 51 of the stepping
motor 52 by means of a spider comprising three radial arms 61 attached to a central
bush 62 fitted to the shaft 51. Such an open-ended construction ensures that the gas
present in its interior does not differ greatly in composition from that in the remainder
of the sampling region 7 in which the hollow member is disposed, and minimizes "crosstalk"
between the various jet generation means.
[0041] Referring next to figure 7, another preferred embodiment of the invention comprises
the jet selection means 83. Two jet generation means 88 and 89 are disposed at 45°
to each other so that their tips are arranged in an arc centered on the axis 37 in
a similar manner to the arrangement illustrated in figure 2. The jet generation means
88, 89 have jet axes 90, 91 respectively. An electrically conductive hollow member
92 comprises four apertures 84-87, arranged in diametrically opposed pairs 86, 84
and 85,87. As can be seen from the figure, as the hollow member 92 is rotated, first
the pair of apertures 86, 84 are aligned with jet axis 90, allowing the jet produced
by the generation means 88 to pass through the sampling region inside the hollow member
92. Further rotation of the hollow member 92 aligns the pair of apertures 85, 87 with
the jet axis 91 and allows the jet formed by jet generation means 89 to pass into
the sampling region. Continued rotation aligns apertures 85, 87 with jet axis 90,
then apertures 84, 86 with jet axis 91, etc. This embodiment is particularly suitable
when only a small number of jet generation means are employed. Its use may increase
the efficiency of the spectrometer because apertures through which a jet may pass
into the sampling region occupy a greater portion of the surface of the hollow member
92. However, it requires a closer spacing of the jet generation means than does the
embodiment shown in figure 2, which is generally preferred if four or more jet generation
means are provided.
[0042] Figure 6 is a highly simplified outline drawing of a tandem mass spectrometer (a
triple quadrupole) according to the invention. The main components of the ion introduction
system, comprising a plurality of charged-particle jet generation means 1, a jet selection
means 4, a sampling cone 6 and an ion guiding means 19, etc, are shown in greater
detail in Figure 1. In place of the orthogonal-acceleration time-of-flight mass analyzer
illustrated in figure 1, a triple quadrupole analyzer is provided. This comprises
a first stage mass-selecting quadrupole 42, a collision cell comprising an RF only
hexapole 43 enclosed in a substantially gas tight enclosure 33, a second-stage mass
analyzing quadrupole 44 and an ion detector 32. The collision cell is used for fragmenting
ions passed to it from the first quadrupole 42. Such triple quadrupole mass analyzers
are well known and need not be described in detail.
[0043] In use, samples present in solutions fed to the charged-particle jet generation means
1 are ionized as previously described. Ions formed from the jet selected at any particular
instant by the selection means 4 pass through the sampling cone 6, hollow conical
member 14 into the triple quadrupole analyzer. Typically, ions having predetermined
mass-to-charge ratios are selected by the first quadrupole 42 and enter the collision
cell 42,33. Here they are fragmented by collisions with inert gas molecules, and the
fragment ions so produced are mass analyzed by the second quadrupole 44. However,
any of the established methods of using a triple quadrupole analyzer may be used.
The operation of the jet selection means 4 and the link between the mass spectral
data generated and the selected jet may be performed as previously described.
1. A mass spectrometer comprising:
an evacuated chamber (8);
a sampling region (7) where in use the pressure is greater than in said evacuated
chamber (8) ;
a sampling orifice (5) communicating between said sampling region (7) and said evacuated
chamber (8) ; and
a mass analyzer (24-27) which receives at least some charged particles which pass
along a first axis (37) through said sampling orifice (5) from said sampling region
(7) into said evacuated chamber (8), said spectrometer being characterized by:
a plurality of charged-particle jet generation means (1, 38-40) each of which is supplied
with a fluid to be analyzed and generates a jet, aligned with a jet axis (3; 45; 46;
47), of charged particles derived from said fluid, disposed so that each generation
means (1, 38-40) has a different jet axis (3, 45-47) and so that all said jet axes
(3, 45-47) intersect said first axis (37) within said sampling region (7);
jet selecting means (4) comprising a hollow member (36) disposed so that the intersections
of said jet axis (3; 45; 46; 47) and said first axis (37) are within its interior,
said hollow member (36) having at least a first aperture (49) alignable with said
jet axis through which at least some charged particles comprised in a said charged-particle
jet may enter the interior of said hollow member (36) and travel to said first axis;
and
means (51-54) for aligning said aperture (49) in said hollow member (36) with each
said jet axis in turn, thereby allowing in turn at least some charged particles comprised
in each said jet to enter the interior of said hollow member (36) to pass through
said sampling orifice (5) to said evacuated chamber (8), and subsequently to enter
said mass analyzer (24-27).
2. The mass spectrometer of claim 1, wherein at least a second aperture (48) is provided
in the hollow member (36) of said jet selecting means (4) through which a charged-particle
jet entering through the first aperture (49) may exit from the interior after intersecting
the first axis (37).
3. The mass spectrometer of claim 1 or 2, wherein at least one of the charged-particle
jet generation means (1; 38; 39; 40) comprises an aerosol generation means maintained
at a high potential relative to counter electrode means disposed downstream of it
in order to generate ions by electrospray ionization.
4. The mass spectrometer of claim 3, wherein said counter electrode means is the hollow
member (36) and the hollow member (36) is made of an electrically conductive material.
5. The mass spectrometer of claims 3 or 4, wherein the aerosol generation means comprises
a capillary tube (72) and means (73, 78) for supplying a nebulizing gas to the exit
of the aerosol generation means to assist the formation of the aerosol.
6. The mass spectrometer of any preceding claim, wherein at least one of the charged-particle
generation means comprises aerosol generation means for generating droplets from said
fluid and means (58) for electrically charging the droplets so produced, in order
to generate ions by atmospheric pressure ionization.
7. The mass spectrometer of claim 6, further comprising an aerosol heating means (59)
for desolvating the droplets produced by the aerosol generating means.
8. The mass spectrometer of claim 6 or 7, wherein the means (58) for electrically charging
the droplets comprises a discharge electrode (58) disposed in said sampling region
(7) and maintained at a potential which results in the formation of a corona discharge.
9. The mass spectrometer of any preceding claim, wherein a heated drying gas is supplied
to the exit of the aerosol generation means in said sampling region (7) to assist
desolvation of droplets in said aerosol.
10. The mass spectrometer of any preceding claim, wherein the charged-particle jet generation
means (1, 38-40) are radially disposed so that the jets they produce are directed
towards said first axis (37), the means (51-54) for aligning said aperture comprising
motor means (52) for rotating said hollow member (36) to bring an aperture (49; 48)
in line with each of the charged-particle jet generation means (1, 38-40) in turn.
11. The mass spectrometer of any preceding claim, wherein the jet selecting means (4)
has a plurality of apertures arranged as diametrically opposed pairs.
12. The mass spectrometer of any preceding claim, wherein the charged-particle jet generation
means (1, 38-40) are disposed around an arc of less than 180° centered on said first
axis (37).
13. The mass spectrometer of any preceding claim, further comprising means for stopping
movement of the hollow member (36) for a predetermined time period when an aperture
(49) in it is aligned with each of the charged-particle jet generation means (1, 38-40)
in turn.
14. The mass spectrometer of any preceding claim, further comprising means for associating
the mass spectral data being acquired at a given time with the charged-particle jet
generation means (1, 38-40) being sampled at that time.
15. The mass spectrometer of any preceding claim, further comprising one or more liquid
chromatographs, each of which feeds at least some of its eluent to a different one
of said plurality of charged-particle jet generation means (1, 38-40).
16. The mass spectrometer of any preceding claim, further comprising one or more capillary
electrophoresis separation devices, each of which feeds at least some of its eluent
to a different one of said plurality of charged-particle jet generation means (1,
38-40).
17. The mass spectrometer of any preceding claim, further comprising means for introducing
a calibration compound into at least one of said charged-particle jet generation means
(1, 38-40).
18. The mass spectrometer of any preceding claim, wherein the mass analyzer comprises
a time-of-flight analyzer (24-27).
19. The mass spectrometer of any of claims 1-17, wherein the mass analyzer comprises a
tandem mass spectrometer (32, 42-44).
20. The mass spectrometer of claim 19, wherein said mass analyzer comprises a triple quadrupole.
21. A method of mass spectrometry comprising mass analyzing charged particles which pass
into an evacuated chamber (8) through a sampling orifice (5) along a first axis (37)
from a sampling region (7) in which the pressure is greater than in the evacuated
chamber (8), said method being
characterized by:
supplying a fluid to be analyzed to each of a plurality of charged-particle jet generation
means (1, 38-40) to generate jets of charged particles derived from said fluid along
a jet axis (3; 45; 46; 47), each said charged-particle jet generation means (1, 38-40)
having a different jet axis (3; 45; 46; 47) and each said jet axis (3; 45; 46; 47)
intersecting said first axis (37) within said sampling region (7); and
selecting in turn each of at least some of the jets of charged-particles by aligning
with them a first aperture (49) in a hollow member (36) within the interior of which
said jet axis (3; 45; 46; 47) and said first axis (37) intersect so that charged particles
comprised in the jet so selected may enter the interior of said hollow member (36)
and travel to said first axis (37) and at least some of said charged-particles pass
along said first axis (37) through said sampling orifice (5) into said evacuated chamber
(8) to be mass analyzed.
22. The method of claim 21, further comprising allowing said selected jet to exit through
a second aperture (48) in said hollow member.
23. The method of claim 21 or 22, wherein at least one of the jets of charged particles
is produced by electrospray ionization.
24. The method of any of claims 21-23, wherein at least one of the jets of charged particles
is produced by atmospheric pressure ionization.
25. The method of any of claims 21-24, wherein the selection of said jets of charged particles
is repeated to repetitively acquire mass spectral data for each selected jet of charged
particles.
26. The method of any of claims 21-25, wherein the mass analyzing comprises measuring
the mass-to-charge ratio of at least some of the charged particles using a time-of-flight
analyzer.
27. The method of any of claims 21-25, wherein the mass analyzing comprises fragmenting
at least some of the ions entering said mass analyzer in a collision cell comprised
in a tandem mass spectrometer.
28. The method of any of claims 21-27, wherein the selecting comprises selecting a jet
of charged particles for a predetermined time by maintaining said hollow member (36)
in a fixed position and acquiring mass spectral data for said predetermined time,
and aligning said hollow member (36) to select the next of said jets of charged particles
for which mass spectral data is acquired, inhibiting the acquisition of data while
said alignment is taking place.
29. The method of any of claims 21-28, wherein the fluid supplied to at least one of the
charged-particle jet generation means (1, 38-40) comprises the eluent from a liquid
chromatograph.
30. The method of any of claims 21-29, wherein the fluid supplied to at least one of the
charged-particle jet generation means (1, 38-40) comprises the eluent from a capillary
electrophoresis separation device.
31. The method of any of claims 21-30, wherein a calibration compound is supplied to one
of said charged-particle jet generation means (1, 38-40).
1. Massenspektrometer, umfassend:
eine Vakuumkammer (8);
einen Probenahmebereich (7), in welchem bei der Verwendung der Druck größer ist als
in der Vakuumkammer (8);
eine Probenahmeöffnung (5) welche eine Verbindung zwischen dem Probenahmebereich (7)
und der Vakuumkammer (8) bildet; und
einen Massenanalysator (24-27), welcher wenigstens einige geladene Partikel aufnimmt,
welche entlang einer ersten Achse (37) durch die Probenahmeöffnung (5) von dem Probenahmebereich
(7) in die Vakuumkammer (8) gelangen, wobei das Spektrometer gekennzeichnet ist durch:
eine Vielzahl von Mitteln zur Erzeugung eines geladene-Partikel-Strahls (1, 38-40),
von denen jedes mit einer zu analysierenden Flüssigkeit versorgt wird und
einen mit einer Strahlachse (3; 45; 46; 47) ausgerichteten Strahl von dieser Flüssigkeit
abgeleiteter geladener Partikel erzeugt, derart angeordnet, dass jedes Erzeugungsmittel
(1, 38-40) eine unterschiedliche Strahlachse (3, 45-47) aufweist, und derart, dass
alle Strahlachsen (3, 45-47) die erste Achse (37) in dem Probenahmebereich (7) schneiden;
Strahlselektionsmittel (4), umfassend ein hohles Element (36), welches derart angeordnet
ist, dass sich die Schnittstellen der Strahlachse (3; 45; 46; 47) und
der ersten Achse (37) in seinem Inneren befinden, wobei das hohle Element (36) wenigstens
eine erste Öffnung (49) aufweist, die mit der Strahlachse ausgerichtet werden kann
und durch welche wenigstens einige in einem geladene-Partikel-Strahl enthaltene geladene Partikel
in das Innere des hohlen Elements (36) eintreten und sich zu der ersten Achse bewegen
können; und
Mittel (51-54) zum aufeinander folgenden Ausrichten der Öffnung (49) in dem hohlen
Element (36) mit jeder Strahlachse, wodurch jeweils ermöglicht wird, dass wenigstens
einige der in jedem geladene-Partikel-Strahl enthaltenen geladenen Partikel in das
Innere des hohlen Elements (36), durch die Probenahmeöffnung (5) zu der Vakuumkammer (8) und nachfolgend in den Massenanalysator
(24-27) eintreten können.
2. Massenspektrometer nach Anspruch 1, wobei wenigstens eine zweite Öffnung (48) in dem
hohlen Element (36) des Strahlselektionsmittels (4) vorgesehen ist, durch welche ein
durch die erste Öffnung (49) eintretender geladene-Partikel-Strahl nach dem Schneiden
der ersten Achse (37) aus dem Inneren austreten kann.
3. Massenspektrometer nach Anspruch 1 oder 2, wobei wenigstens eines der Mittel zur Erzeugung
eines geladene-Partikel-Strahls (1, 38; 39; 40) ein Aerosolerzeugungsmittel umfasst,
das in Bezug zu einem Gegenelektrodenmittel, welches zu ihm stromabwärts angeordnet
ist, auf einem hohen Potenzial gehalten wird, um Ionen durch Elektrospray-Ionisierung
zu erzeugen.
4. Massenspektrometer nach Anspruch 3, wobei das Gegenelektrodenmittel ein hohles Element
(36) ist und wobei das hohle Element (36) aus einem elektrisch leitenden Material
gebildet ist.
5. Massenspektrometer nach den Ansprüchen 3 oder 4, wobei das Aerosolerzeugungsmittel
ein Kapillarrohr (72) sowie Mittel (73, 78) zum Leiten eines Vernebelungsgases zum
Ausgang des Aerosolerzeugungsmittels umfasst, um die Bildung eines Aerosols zu unterstützen.
6. Massenspektrometer nach einem der vorangehenden Ansprüche, wobei wenigstens eines
der Mittel zur Erzeugung geladener Partikel ein Aerosolerzeugungsmittel zum Erzeugen
von Tröpfchen aus der Flüssigkeit sowie Mittel (58) für das elektrische Laden der
so erzeugten Tröpfchen umfasst, um Ionen durch Atmosphärendruck-Ionisierung zu erzeugen.
7. Massenspektrometer nach Anspruch 6, welches ferner ein Aerosolerwärmungsmittel (59)
für die Desolvation der durch das Aerosolerzeugungsmittel erzeugten Tröpfchen umfasst.
8. Massenspektrometer nach Anspruch 6 oder 7, wobei das Mittel (58) zum elektrischen
Laden der Tröpfchen eine Entladungselektrode (58) umfasst, welche in dem Probenahmebereich
(7) angeordnet ist und auf einem Potenzial gehalten wird; das zur Bildung einer Glimmentladung
führt.
9. Massenspektrometer nach einem der vorangehenden Ansprüche, wobei ein erwärmtes Trockengas
zu dem Ausgang des Aerosolerzeugungsmittels in dem Probenahmebereich (7) geleitet
wird, um die Desolvation der Tröpfchen in dem Aerosol zu unterstützen.
10. Massenspektrometer nach einem der vorangehenden Ansprüche, wobei die Mittel zur Erzeugung
eines geladene-Partikel-Strahls (1, 38-40) radial angeordnet sind, so dass die von
ihnen erzeugten Strahlen zu der ersten Achse (37) hin gerichtet sind, wobei das Mittel
(51-54) zum Ausrichten der Öffnung ein Motormittel (52) zum Drehen des hohlen Elements
(36) umfasst, um eine Öffnung (49; 48) aufeinander folgend mit jedem der Mittel zur
Erzeugung eines geladene-Partikel-Strahls (1, 38-40) in Reihe zu bringen.
11. Massenspektrometer nach einem der vorangehenden Ansprüche, wobei das Strahlselektionsmittel
(4) eine Vielzahl von Öffnungen umfasst, die als diametral entgegen gesetzte Paare
angeordnet sind.
12. Massenspektrometer nach einem der vorangehenden Ansprüche, wobei die Mittel zur Erzeugung
eines geladene-Partikel-Strahls (1, 38-40) um einen auf die erste Achse (37) zentrierten
Bogen von weniger als 180° herum angeordnet sind.
13. Massenspektrometer nach einem der vorangehenden Ansprüche, welches ferner Mittel zum
Anhalten der Bewegung des hohlen Elements (36) über einen vorbestimmten Zeitraum umfasst,
wenn eine Öffnung (49) darin aufeinader folgend mit jedem der Mittel zur Erzeugung
eines geladene-Partikel-Strahls (1, 38-40) ausgerichtet ist.
14. Massenspektrometer nach einem der vorangehenden Ansprüche, welches ferner Mittel umfasst,
um die zu einem bestimmten Zeitpunkt erhobenen Massenspektraldaten in Verbindung zu
den zu diesem Zeitpunkt abgefragten Mitteln zur Erzeugung eines geladene-Partikel-Strahls
(1, 38-40) zu setzen.
15. Massenspektrometer nach einem der vorangehenden Ansprüche, welches ferner einen oder
mehrere Flüssigchromatographen umfasst, wobei jeder wenigstens einen Teil seines Elutionsmittels
einem anderen der Vielzahl von Mitteln zur Erzeugung eines geladene-Partikel-Strahls
(1, 38-40) zuführt.
16. Massenspektrometer nach einem der vorangehenden Ansprüche, welches ferner eine oder
mehrere Kapillarelektrophorese-Trennungsvorrichtungen umfasst, von denen jede wenigstens
einen Teil ihres Elutionsmittels einem anderen der Vielzahl von Mitteln zur Erzeugung
eines geladene-Partikel-Strahls (1, 38-40) zuführt.
17. Massenspektrometer nach einem der vorangehenden Ansprüche, welches ferner Mittel zum
Einführen einer Kalibrierungskomponente in wenigstens eines der Mittel zur Erzeugung
eines geladene-Partikel-Strahls (1, 38-40) umfasst.
18. Massenspektrometer nach einem der vorangehenden Ansprüche, wobei der Massenanalysator
einen Flugzeitanalysator (24-27) umfasst.
19. Massenspektrometer nach einem der Ansprüche 1-17, wobei der Massenanalysator ein Tandem-Massenspektrometer
(32, 42-44) umfasst.
20. Massenspektrometer nach Anspruch 19, wobei der Massenanalysator einen dreifachen Quadrupol
umfasst.
21. Verfahren der Massenspektrometrie, umfassend die Massenanalyse geladener Partikel,
die in eine Vakuumkammer (8) durch eine Probenahmeöffnung (5) entlang einer ersten
Achse (37) von einem Probenahmebereich (7) eintreten, in welchem der Druck größer
ist als in der Vakuumkammer (8), wobei das Verfahren
gekennzeichnet ist durch:
das Versorgen einer Vielzahl von Mitteln zur Erzeugung eines geladene-Partikel-Strahls
(1, 38-40) mit einer zu analysierenden Flüssigkeit zum Erzeugen von von dieser Flüssigkeit
abgeleiteten geladene-Partikel-Strahlen entlang einer Strahlachse (3; 45; 46; 47),
wobei jedes Mittel zur Erzeugung eines geladene-Partikel-Strahls (1, 38-40) eine unterschiedliche
Strahlachse (3; 45; 46; 47) aufweist und wobei jede Strahlachse (3; 45; 46; 47) die
erste Achse (37) in dem Probenahmebereich (7) schneidet; und
aufeinander folgendes Selektieren jedes der wenigstens einigen geladene-Partikel-Strahlen
durch Ausrichten einer ersten Öffnung (49) in einem hohlen Element (36), in dessen Inneren
sich die Strahlachse (3; 45; 46; 47) und die erste Achse (37) schneiden, mit den Strahlen,
so dass derart selektierte, in dem Strahl enthaltene geladene Partikel in das Innere
des hohlen Elements (36) eintreten können und zu der ersten Achse (37) gelangen können
und so dass wenigstens einige der geladenen Partikel für die Massenanalyse entlang
der ersten Achse (37) durch die Probenöffnung (5) in die Vakuumkammer (8) gelangen.
22. Verfahren nach Anspruch 21, welches ferner umfasst, dass der selektierte Strahl durch
eine zweite Öffnung (48) in dem hohlen Element austreten kann.
23. Verfahren nach Anspruch 21 oder 22, wobei wenigstens einer der geladene-Partikel-Strahlen
durch Elektrospray-lonisierung erzeugt wird.
24. Verfahren nach Anspruch 21-23, wobei wenigstens einer der geladene-Partikel-Strahlen
durch Atmosphärendurck-Ionisierung erzeugt wird.
25. Verfahren nach einem der Ansprüche 21-24, wobei die Selektion der geladene-Partikel-Strahlen
wiederholt wird, um repetitiv Massenspektraldaten für jeden selektierten geladene-Partikel-Strahl
zu erhalten.
26. Verfahren nach einem der Ansprüche 21-25, wobei die Massenanalyse das Messen des Masse-zu-Ladung-Verhältnisses
von wenigstens einigen der geladenen Partikel unter Verwendung eines Flugzeit-Analysators
umfasst.
27. Verfahren nach einem der Ansprüche 21-25, wobei die Massenanalyse das Fragmentieren
von wenigstens einigen der Ionen umfasst, die in den Massenanalysator in einer in
einem Tandem-Massenspektrometer angeordneten Kollisionszelle gelangen.
28. Verfahren nach einem der Ansprüche 21-27, wobei die Selektion das Selektieren eines
geladene-Partikel-Strahls über eine vorbestimmte Zeit durch Beibehalten des hohlen
Elements (36) in einer festen Position und das Erfassen von Massenspektraldaten für
diese vorbestimmte Zeit umfasst, sowie das Ausrichten des hohlen Elements (36) zum
Selektieren des nächsten geladene-Partikel-Strahls, für welchen Massenspektraldaten
erfasst werden, wobei die Erfassung von Daten verhindert wird, während die Ausrichtung
stattfindet.
29. Verfahren nach einem der Ansprüche 21-28, wobei die wenigstens einem der Mittel zur
Erzeugung eines geladene-Partikel-Strahls (1, 38-40) zugeführte Flüssigkeit das Elutionsmittel
eines Flüssigchromatographen umfasst.
30. Verfahren nach einem Ansprüche 21-29, wobei die wenigstens einem der Mittel zur Erzeugung
eines geladene-Partikel-Strahls (1, 38-40) zugeführte Flüssigkeit das Elutionsmittel
einer Kapillarelektrophorese-Trennungsvorrichtung umfasst.
31. Verfahren nach einem der Ansprüche 21-30, wobei eine Kalibrierungskomponente einem
der Mittel zur Erzeugung eines geladene-Partikel-Strahls (1, 38-40) zugeführt wird.
1. Spectromètre de masse, comprenant:
une chambre à vide (8);
un région d'échantillonnage (7) dans laquelle, en service, la pression est supérieure
à la pression régnant dans ladite chambre à vide (8);
un orifice d'échantillonnage (5) établissant une communication entre ladite région
d'échantillonnage (7) et ladite chambre à vide (8); et
un analyseur de masse (24-27) qui reçoit au moins plusieurs particules chargées qui
passent le long d'un premier axe (37) à travers ledit orifice d'échantillonnage (5)
à partir de ladite région d'échantillonnage (7) dans ladite chambre à vide (8), ledit
spectromètre étant caractérisé par:
une pluralité de moyens de génération de jets de particules chargées (1, 38-40), chacun
de ceux-ci étant alimenté par un fluide à analyser et générant un jet, aligné avec
un axe de jet (3; 45; 46; 47), de particules chargées dérivées dudit fluide, disposés
de telle sorte que chaque moyen de génération (1, 38-40) présente un axe de jet différent
(3, 45-47) et de telle sorte que chacun desdits axes de jet (3, 45-47) coupe ledit
premier axe (37) à l'intérieur de ladite région d'échantillonnage (7);
des moyens de sélection de jet (4) comprenant un élément creux (36) disposé de telle
sorte que les intersections dudit axe de jet (3; 45; 46; 47) et dudit premier axe
(37) se trouvent à l'intérieur de son volume intérieur, ledit élément creux (36) comportant
au moins une première ouverture (49) qui peut être alignée avec ledit axe de jet à
travers laquelle au moins plusieurs particules chargées présentes dans un desdits
jets de particules chargées peuvent entrer à l'intérieur dudit élément creux (36)
et se déplacer vers ledit premier axe; et
des moyens (51-54) pour aligner ladite ouverture (49) dans ledit élément creux (36)
avec chacun desdits axes de jet tour à tour, permettant ainsi à au moins plusieurs
particules chargées présentes dans chacun desdits jets d'entrer à leur tour à l'intérieur
dudit élément creux (36) pour passer à travers ledit orifice d'échantillonnage (5)
jusqu'à ladite chambre à vide (8), et ensuite d'entrer dans ledit analyseur de masse
(24-27).
2. Spectromètre de masse selon la revendication 1, dans lequel au moins une deuxième
ouverture (48) est prévue dans l'élément creux (36) desdits moyens de sélection de
jet (4), à travers laquelle un jet de particules chargées qui entre à travers la première
ouverture (49) peut sortir hors du volume intérieur après l'intersection avec le premier
axe (37).
3. Spectromètre de masse selon la revendication 1 ou 2, dans lequel au moins un des moyens
de génération de jets de particules chargées (1; 38; 39; 40) comprend des moyens de
génération d'aérosol maintenus à un potentiel élevé par rapport à un moyen de contre-électrode
disposé en aval de celui-ci pour générer des ions par ionisation par électro-pulvérisation.
4. Spectromètre de masse selon la revendication 3, dans lequel ledit moyen de contre-électrode
est l'élément creux (36), et l'élément creux (36) est constitué d'une matière électriquement
conductrice.
5. Spectromètre de masse selon la revendication 3 ou 4, dans lequel les moyens de génération
d'aérosol comprennent un tube capillaire (72) et des moyens (73, 78) pour fournir
un gaz nébulisant à la sortie des moyens de génération d'aérosol destiné à aider la
formation de l'aérosol.
6. Spectromètre de masse selon l'une quelconque des revendications précédentes, dans
lequel au moins un des moyens de génération de jets de particules chargées comprend
des moyens de génération d'aérosol pour générer des gouttelettes à partir dudit fluide,
et un moyen (58) pour charger électriquement les gouttelettes ainsi produites, en
vue de générer des ions par ionisation à la pression atmosphérique.
7. Spectromètre de masse selon la revendication 6, comprenant en outre un moyen de chauffage
d'aérosol (59) pour dissoudre les gouttelettes produites par les moyens de génération
d'aérosol.
8. Spectromètre de masse selon la revendication 6 ou 7, dans lequel le moyen (58) pour
charger électriquement les gouttelettes comprend une électrode de décharge (58) disposée
dans ladite région d'échantillonnage (7) et maintenue à un potentiel qui entraîne
la formation d'une décharge corona.
9. Spectromètre de masse selon l'une quelconque des revendications précédentes, dans
lequel un gaz de séchage chauffé est fourni à la sortie des moyens de génération d'aérosol
dans ladite région d'échantillonnage (7) pour aider la dissolution des gouttelettes
dans ledit aérosol.
10. Spectromètre de masse selon l'une quelconque des revendications précédentes, dans
lequel les moyens de génération de jets de particules chargées (1, 38-40) sont disposés
radialement de telle sorte que les jets qu'ils produisent soient dirigés vers ledit
premier axe (37), les moyens (51-54) pour aligner ladite ouverture comprenant un moyen
de moteur (52) pour faire tourner ledit élément creux (36) pour amener une ouverture
(49; 48) en ligne avec chacun des moyens de génération de jets de particules chargées
(1, 38-40) tour à tour.
11. Spectromètre de masse selon l'une quelconque des revendications précédentes, dans
lequel lesdits moyens de sélection de jet (4) comprennent une pluralité d'ouvertures
arrangées par paires diamétralement opposées.
12. Spectromètre de masse selon l'une quelconque des revendications précédentes, dans
lequel les moyens de génération de jets de particules chargées (1, 38-40) sont disposés
autour d'un arc inférieur à 180° centré sur ledit premier axe (37).
13. Spectromètre de masse selon l'une quelconque des revendications précédentes, comprenant
en outre des moyens pour arrêter le déplacement de l'élément creux (36) pendant une
période de temps prédéterminée lorsqu'une ouverture (49) dans celui-ci est alignée
avec chacun des moyens de génération de jets de particules chargées (1, 38-40) tour
à tour.
14. Spectromètre de masse selon l'une quelconque des revendications précédentes, comprenant
en, outre des moyens pour associer les données spectrales de masse acquises à un moment
donné avec les moyens de génération de jets de particules chargées (1, 38-40) échantillonnés
à cet instant.
15. Spectromètre de masse selon l'une quelconque des revendications précédentes, comprenant
en outre un ou plusieurs chromatographe(s) liquide(s), chacun de ceux-ci fournissant
au moins une partie de son éluant à un moyen de génération de jets de particules chargées
différent de ladite pluralité de moyens de génération de jets de particules chargées
(1, 38-40).
16. Spectromètre de masse selon l'une quelconque des revendications précédentes, comprenant
en outre un ou plusieurs dispositif(s) de séparation par électrophorèse capillaire,
chacun de ceux-ci fournissant au moins une partie de son éluant à un moyen de génération
de jets de particules chargées différent de ladite pluralité de moyens de génération
de jets de particules chargées (1, 38-40).
17. Spectromètre de masse selon l'une quelconque des revendications précédentes, comprenant
en outre des moyens pour introduire un composé de calibrage dans au moins un desdits
moyens de génération de jets de particules chargées (1, 38-40).
18. Spectromètre de masse selon l'une quelconque des revendications précédentes, dans
lequel l'analyseur de masse comprend un analyseur de temps de vol (24-27).
19. Spectromètre de masse selon l'une quelconque des revendications 1 à 17, dans lequel
l'analyseur de masse comprend un spectromètre de masse tandem (32, 42-44).
20. Spectromètre de masse selon la revendication 19, dans lequel ledit analyseur de masse
comprend un triple quadripôle.
21. Procédé de spectrométrie de masse, comprenant une analyse de masse de particules chargées
qui passent dans une chambre à vide (8) à travers un orifice d'échantillonnage (5)
le long d'un premier axe (37) en provenance d'une région d'échantillonnage (7) dans
laquelle la pression est supérieure à celle régnant dans la chambre à vide (8), ledit
procédé étant
caractérisé par:
la fourniture d'un fluide à analyser à chacun d'une pluralité de moyens de génération
de jets de particules chargées (1, 38-40) pour générer des jets de particules chargées
dérivées dudit fluide le long d'un axe de jet (3; 45; 46; 47), chacun desdits moyens
de génération de jets de particules chargées (1, 38-40) présentant un axe de jet différent
(3; 45; 46; 47), et chacun desdits axes de jet (3; 45; 46; 47) coupant ledit premier
axe (37) à l'intérieur de ladite région d'échantillonnage (7); et
la sélection tour à tour de chacun d'au moins plusieurs des jets de particules chargées
en alignant avec ceux-ci une première ouverture (49) dans un élément creux (36) à
l'intérieur du volume intérieur duquel ledit axe de jet (3; 45; 46; 47), et ledit
premier axe (37) se coupent de telle sorte que les particules chargées présentes dans
le jet ainsi sélectionné puissent entrer à l'intérieur dudit élément creux (36) et
se déplacer vers ledit premier axe (37), et qu'au moins plusieurs desdites particules
chargées passent le long dudit premier axe (37) à travers ledit orifice d'échantillonnage
(5) dans ladite chambre à vide (8) pour y subir une analyse de masse.
22. Procédé selon la revendication 21, comprenant en outre l'octroi d'une autorisation
audit jet sélectionné de sortir à travers une deuxième ouverture (48) dans ledit élément
creux.
23. Procédé selon la revendication 21 ou 22, dans lequel au moins un des jets de particules
chargées est produit par ionisation par électro-pulvérisation.
24. Procédé selon l'une quelconque des revendications 21 à 23, dans lequel au moins un
des jets de particules chargées est produit par ionisation à la pression atmosphérique.
25. Procédé selon l'une quelconque des revendications 21 à 24, dans lequel la sélection
desdits jets de particules chargées est répétée pour acquérir sélectivement des données
spectrales de masse pour chaque jet sélectionné de particules chargées.
26. Procédé selon l'une quelconque des revendications 21 à 25, dans lequel l'analyse de
masse comprend la mesure d'un rapport masse - charge d'au moins une partie des particules
chargées en utilisant un analyseur de temps de vol.
27. Procédé selon l'une quelconque des revendications 21 à 25, dans lequel l'analyse de
masse comprend la fragmentation d'au moins certains des ions qui entrent dans ledit
analyseur de masse dans une cellule de collision formée dans un spectromètre de masse
tandem.
28. Procédé selon l'une quelconque des revendications 21 à 27, dans lequel la sélection
comprend la sélection d'un jet de particules chargées pendant une période de temps
prédéterminée en maintenant ledit élément creux (36) dans une position fixe et en
acquérant des données spectrales de masse pendant ladite période de temps prédéterminée,
et l'alignement dudit élément creux (36) pour sélectionner le jet de particules chargées
suivant desdits jets de particules chargées pour lequel lesdites données spectrales
de masse sont acquises, et l'empêchement de l'acquisition de données pendant que ledit
alignement est réalisé.
29. Procédé selon l'une quelconque des revendications 21 à 28, dans lequel le fluide fourni
à au moins un des moyens de génération de jets de particules chargées (1, 38-40) comprend
l'éluant en provenance d'un chromatographe liquide.
30. Procédé selon l'une quelconque des revendications 21 à 29, dans lequel le fluide transmis
à au moins un des moyens de génération de jets de particules chargées (1, 38-40) comprend
l'éluant en provenance d'un dispositif de séparation par électrophorèse capillaire.
31. Procédé selon l'une quelconque des revendications 21 à 30, dans lequel un composé
de calibrage est introduit dans l'un desdits moyens de génération de jets de particules
chargées (1, 38-40).